Medical Systems, Methods, and Devices for Hypopigmentation Cooling Treatments

ABSTRACT

Embodiments of the present invention generally relate to methods, devices, and systems for reducing a pigmentation of a skin of a patient. In some embodiments, freezing of the skin may be desirable to effect the hypopigmentation of the skin of the patient. Generally, embodiments may limit supercooling (or promote freezing) of the skin of the patient during a cooling treatment. In some embodiments, coupling fluids are provided to reduce a thermal contact resistance between a cooling treatment probe and the skin of the patient to improve cooling treatment. Optionally, a fluid carrier may be provided to help retain the coupling fluid at the treatment site. In some embodiments, the coupling fluid may include ice nucleating agents to promote ice crystal formation in the coupling fluid during cooling treatment. The ice crystal formation in the coupling fluid may progress into the skin to limit supercooling of the skin during treatment.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of and priority to U.S.Provisional Patent Application 62/214,446 filed Sep. 4, 2015, thecontents of which are incorporated herein in their entirety for allpurposes.

BACKGROUND

Embodiments of the present invention generally relate to methods,devices, and systems for reducing a pigmentation of a skin of a patient.More specifically, embodiments generally relate to methods, devices, andsystems to increase the chance of freezing (water phase transition) inthe skin.

Controlled freezing of biological tissue, such as skin tissue, canproduce various effects. Certain tissue freezing procedures and devices,such as conventional cryoprobes, can cause severe freezing of tissue andgenerate cellular damage. It has been observed that moderate degrees offreezing can produce particular effects, such as affecting theexpression of skin pigmentation.

There is a demand for cosmetic products that can lighten the appearanceof skin or otherwise controllably affect skin pigmentation. For example,it may be desirable to lighten the overall complexion or color of aregion of skin to alter the general appearance for cosmetic reasons.Also, lightening of particular hyperpigmented regions of skin, such aslarge freckles, ‘café au lait’ spots, melasma, or dark circles under theeyes that may result from excessive local amounts of pigment in theskin, may also be desirable for cosmetic reasons. Hyperpigmentation canresult from a variety of factors such as UV exposure, aging, stress,trauma, inflammation, etc. Such factors can lead to an excess productionof melanin, or melanogenesis, in the skin by melanocytes, which can leadto formation of hyperpigmented areas. Such hyperpigmented areas aretypically associated with excess melanin within the epidermis; however,they can also result from excess melanin deposited within the dermis.

Hypopigmentation of skin tissue has been observed as a side effect inresponse to temporary cooling or freezing of the tissue, such as mayoccur during cryosurgery procedures. Loss of pigmentation following skincooling or freezing may result from decreased melanin production,decreased melanosome production, destruction of melanocytes, orinhibited transfer of melanosome into the keratinocytes in the lowerregion of the epidermal layer. The resultant hypopigmentation may belong-lasting or permanent. However, it has also been observed that someof these freezing procedures can generate regions of hyperpigmentationof skin tissue. The level of increase or decrease in pigmentation may bedependent upon certain aspects of the cooling or freezing conditions,including the temperature of the cooling treatment, and the length oftime the tissue is exposed to freezing conditions.

While some hypopigmentation treatments, devices, and systems have beenpreviously developed, further improvements may be desired. Toward thisend, it may be desirable to improve the consistency of skin freezing andthe consistency of a duration of skin freezing. Such improvements may bedesirable to improve overall hypopigmentation consistency. For example,with some cooling treatments, the skin may sometimes freeze toward thebeginning of the cooling treatment, or may sometimes cool to atemperature below the freezing point (e.g., 0 to −5° C.) for a periodand then freeze thereafter. With some cooling treatments, the skin maybecome supercooled (cooled to a temperature below the freezing point)and may not freeze at all during the cooling treatment. Such variabilityin the skin freezing (i.e., the formation of water ice in the skin) mayresult in less than optimal treatment.

In light of the above, it may be desirable to improve the consistency orrepeatability of hypopigmentation treatments, in particularhypopigmentation treatments provided via skin freezing. At least someembodiments of the present invention may provide additional control overthe occurrence of freezing and may limit supercooling or otherwisepromote freezing of the skin during a cooling treatment.

SUMMARY OF THE INVENTION

The present invention generally relates to improved medical devices,systems, and methods, with exemplary embodiments providing improvedcooling treatment probes and cooling treatment methods and systems. Insome embodiments, freezing of the skin may be desirable to effect thehypopigmentation of the skin of the patient. Generally, embodiments maylimit supercooling or otherwise promote freezing of the skin of thepatient during a cooling treatment. In some embodiments, coupling fluidsare provided to reduce a thermal contact resistance between a coolingtreatment probe and the skin of the patient to improve coolingtreatment. Optionally, a fluid carrier may be provided to help retainthe coupling fluid at the treatment site. In some embodiments, thecoupling fluid may include ice nucleating agents to promote ice crystalformation in the coupling fluid during cooling treatment. The icecrystal formation in the coupling fluid may progress into the skin tolimit supercooling or otherwise promote freezing of the skin duringtreatment.

Some aspects of the present invention may provide a method of altering apigmentation and/or melanin of a skin of a patient. For example, someembodiments may lighten the skin of a patient (i.e., hypopigmentation).The method may include applying a coupling fluid to a treatment area onthe skin of the patient. The coupling fluid may include an icenucleating agent configured to promote ice formation in the couplingfluid. A cooling treatment may be applied to the treatment area with theapplied coupling fluid present. The cooling treatment and ice nucleatingagent may promote ice crystal formation in the coupling fluid. The icecrystal formation in the coupling fluid may propagate into the skin ofthe patient and limit supercooling or otherwise promote freezing of theskin of the patient during the cooling treatment.

The ice nucleating agent may be organic or inorganic. Optionally, theice nucleating agents are inorganic materials such as soot, dust, fineparticulates (microparticles, nanoparticles, or the like), or silveriodide, silver oxide, or alumina crystals. Other ice nucleatingmaterials that can be added to the coupling fluid may be organicsubstances such as proteins, lipoproteins, bacteria or fungi. Long chainaliphatic alcohols and amino acids, such as 1-aspartic acid can also beadded to the coupling fluid (e.g., water). In some embodiments, thecoupling fluid may have a freezing point near 0° C., to help reduce orlimit the chance of supercooling in the tissue.

In some embodiments, the method may further include abrading or piercingthe treatment area prior to applying the cooling treatment. The abradingor piercing of the treatment area may be performed by abrading orpiercing the treatment area using a microderm abrasion roller or alaser. The abrasion or piercing of the treatment area may facilitate icecrystal formation or propagation into the skin of the patient.

Optionally, the coupling fluid may be applied to the treatment area onthe skin of the patient by applying a fluid carrier to the treatmentarea of the skin. The fluid carrier may be pre-saturated with a fluidand may be configured to retain the coupling fluid at the treatmentarea. In some embodiments, the fluid carrier has a uniform thickness.The fluid carrier may be a woven or nonwoven fabric material. In someembodiments, the coupling fluid may be an aqueous fluid including athickening agent that increases viscosity of the aqueous fluid. Thethickening agent may help retain the coupling fluid at the treatmentsite.

The cooling treatment may be applied by contacting a treatment surfaceof a cooling probe with the coupling fluid at the treatment site.Optionally, the cooling probe may include a vibrator for triggering orotherwise facilitate ice formation by applying vibrations to thetreatment area of the skin. The vibrator may be an acoustic transducer,an ultrasound transducer, or a motor with an eccentric weight forexample. In some embodiments, the cooling treatment may be applied bycontacting a treatment surface of a cooling probe with the couplingfluid at the treatment site where the treatment surface of the coolingprobe comprises a textured or rough surface (e.g., knurled surface orthe like) having recessed areas configured to retain ice crystals. Thesurface may have a roughness between 32-256 μm (micro inches). In someembodiments, the surface may alternatively have a roughness of 1000-2000μm or greater. Surface roughness or Ra (average surface roughness) is atypical part call-out and can be measured by standard metrologytechniques including with a profilometer which has a stylus that isdragged along the surface and measures local height variations of thesurface.

In further aspects of the present invention, a method of alteringpigmentation of skin of a patient may be provided that may includeapplying a fluid carrier to a treatment area on the skin of the patientand infusing the fluid carrier with a coupling fluid. Thereafter acooling treatment may be applied to the treatment area of the skin topromote ice crystal formation in the coupling fluid retained by thefluid carrier. The ice crystal formation in the coupling fluid maypropagate into the skin of the patient and may limit supercooling orotherwise promote freezing of the skin of the patient during the coolingtreatment. Optionally, the skin may be abraded or pierced prior toapplying the cooling treatment. The fluid carrier may have a uniformthickness. The fluid carrier may be a fabric material (e.g., gauze orthe like).

In yet another aspect of the invention, a method of alteringpigmentation of a target area of a skin of a patient may be providedthat may include abrading or piercing the epidermis layer of a skindefining a target area and applying a coupling fluid to the target areaon the skin of the patient. A cooling treatment may be applied to thetreatment area with the applied coupling fluid present. The coolingtreatment may promote ice crystal formation in the coupling fluid andthe ice crystal formation in the coupling fluid may propagate into theskin of the patient and limit supercooling or otherwise promote freezingof the skin of the patient during the cooling treatment.

In further aspects, a method of altering pigmentation of a skin of apatient may be provided. The method may include pre-treating a contactsurface of a cooling treatment probe by misting a liquid on the contactsurface. The contact surface of the cooling treatment probe may be at atemperature below a freezing point of the liquid. Accordingly, themisted liquid may form ice crystals on the contact surface of thecooling treatment probe. A fluid carrier may be applied to a treatmentarea on the skin of the patient. Thereafter, the pretreated contactsurface of the cooling treatment probe with the ice crystals may becontacted with the coupling fluid at the treatment site. The coolingtreatment probe in addition to the ice crystals formed by thepretreatment may promote ice crystal formation in the coupling fluid.The ice crystal formation in the coupling fluid may propagate into theskin of the patient and may limit supercooling or otherwise promotefreezing of the skin of the patient during the cooling treatment.

Additional embodiments of the present invention may provide a system foraltering pigmentation of a skin of a patient. The system may include acooling treatment probe. The cooling treatment probe may include acontact surface for contacting a treatment area of the skin of thepatient with a coupling fluid present at the treatment area. The contactsurface may have a textured surface having recessed areas configured topromote ice crystal formation in the coupling fluid during a coolingtreatment. The ice crystal formation in the coupling fluid may beconfigured to propagate into the skin of the patient to limitsupercooling or otherwise promote freezing of the skin of the patientduring cooling treatment.

In some embodiments, the cooling treatment probe may include a vibratorfor vibrating the contact surface of the cooling treatment probe totrigger or otherwise facilitate ice formation. The vibrator may be anultrasound transducer or the like.

The system may include the coupling fluid. The coupling fluid mayinclude an ice nucleating agent for application to the treatment area ofthe skin of the patient. The ice nucleating agent may be a bacteria, afungi, soot, dust, a protein, lipoprotein, or a long-chain aliphaticalcohol or amino acid or the like. A fluid carrier may be provided forapplication to the treatment area and for retaining coupling fluid atthe treatment area. The fluid carrier may have a uniform thickness. Thefluid carrier may be a fabric material (e.g., gauze, cloth, or thelike).

In additional aspects, a system for altering pigmentation of skin of apatient may be provided that includes a fluid carrier configured to beapplied to a treatment area of the skin. The fluid carrier may beconfigured to be infused with a coupling fluid and to retain thecoupling fluid at the treatment area of the skin. A cooling treatmentprobe may be provided that includes a contact surface for contacting thefluid carrier. The contact surface of the cooling treatment probeconfigured to promote ice crystal formation in the coupling fluidretained in the fluid carrier. Optionally, the fluid carrier may have auniform thickness and may be made of a fabric material.

In further aspects, a system for altering pigmentation of a skin of apatient may be provided that includes a cooling treatment probecomprising a contact surface for contacting a treatment area of the skinof the patient with a coupling fluid present at the treatment area. Avibrator may be provided for vibrating the contact surface of thecooling treatment probe to trigger or otherwise facilitate ice formationin the coupling fluid during a cooling treatment. The ice crystalformation in the coupling fluid may be configured to propagate into theskin of the patient to limit supercooling or otherwise promote freezingof the skin of the patient during cooling treatment. In at least someembodiments, the vibrator may be an ultrasound transducer.

Embodiments of the invention covered by this patent are defined by theclaims below, not this summary. This summary is a high-level overview ofvarious aspects of the invention and introduces some of the conceptsthat are further described in the Detailed Description section below.This summary is not intended to identify key or essential features ofthe claimed subject matter, nor is it intended to be used in isolationto determine the scope of the claimed subject matter. The subject mattershould be understood by reference to appropriate portions of the entirespecification of this patent, any or all drawings, and each claim.

The invention will be better understood upon reading the followingdescription and examining the figures which accompany it. These figuresare provided by way of illustration only and are in no way limiting onthe invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Further details, aspects, and embodiments of the invention will bedescribed by way of example only and with reference to the drawings. Inthe drawings, like reference numbers are used to identify like orfunctionally similar elements. Elements in the figures are illustratedfor simplicity and clarity and have not necessarily been drawn to scale.

FIG. 1 illustrates an exemplary method according to some embodiments ofthe present invention.

FIG. 2A is an exemplary cross-sectional side view of an exemplaryapparatus that can be used to produce hypopigmentation in a skin tissueaccording to exemplary embodiments of the present invention.

FIG. 2B is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2C is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2D is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2E is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2F is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2G is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2H is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2I is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2J is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 2K is a bottom view of an exemplary configuration of the contactelement of the apparatus of FIG. 2A according to some embodiments.

FIG. 3 illustrates the application of a fluid carrier to a treatmentarea of a skin of a patient according to some embodiments of the presentinvention.

FIG. 4 illustrates the application of a coupling fluid having icenucleating agents or thickening agents to a treatment area according tosome embodiments of the present invention.

FIG. 5 illustrates a cooling treatment applied by an exemplary coolingtreatment probe to freeze at least a portion of the treatment area ofthe skin according to some embodiments of the present invention.

FIG. 6 illustrates a reduction in melanin and/or melanocytes in the toplayer of the skin according to some embodiments of the presentinvention.

FIG. 7 illustrates exemplary abrasion or piercing of the target area ofthe skin of the patient prior to treatment according to some embodimentsof the present invention.

FIG. 8 illustrates the application of a coupling fluid (with or withoutice nucleating agents and/or thickening agents) to the treatment area ofthe skin according to some embodiments of the present invention.

FIG. 9 illustrates a cooling treatment applied by an exemplary coolingtreatment probe to freeze at least a portion of the treatment area ofthe skin of the patient according to some embodiments of the presentinvention.

FIG. 10 illustrates a reduction in melanin and/or melanocytes in the toplayer of the skin according to some embodiments of the presentinvention.

FIG. 11 illustrates an cross-sectional side view of an exemplary coolingtreatment apparatus that can be used to produce hypopigmentation in askin tissue according to some embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

As set forth above, some embodiments of the present invention may bedirected to techniques to affect melanocytes of a patient. For example,some embodiments may be directed to methods and systems for reducingskin pigmentation by cooling the skin of a patient. In some embodimentsit may be beneficial to freeze the skin. Additionally, it may beadvantageous to freeze the skin in a more controllable and consistentmanner. The freezing event, although it may not be required, has beenshown to have an effect on both the desired outcome of reducedpigmentation, but also the short term side effects of epidermal necrosisand in some cases prolonged erythema and hyperpigmentation. In previousstudies, the timing of skin freezing has been found to be inconsistent.Different results (time to freezing, or lack of freezing) have been seenwhen replicates of the same treatment parameters are performed.Accordingly, some embodiments of the present invention provide increasedcontrol over the occurrence of freezing in the skin of a patient and maylimit supercooling or otherwise promote freezing in the skin. Methodsand systems described herein may thus increase the chance,predictability, and/or consistency of freezing in the skin of a patient(e.g., repeatable freezing at certain temperatures and/or cooling rates)and may thereby provide additional control over a duration of skinfreezing during treatment. Some embodiments may be directed to limitingsupercooling or otherwise promote freezing of the skin of a patientduring a cooling treatment. Supercooling of the skin may be cooling ofthe skin below the water freezing point without solidification orcrystallization of water in the skin.

A number of cooling systems have been developed for lightening thepigmentation of skin (see e.g., U.S. Patent Publication 2011/0313411;U.S. Patent Publication 2014/0303696; U.S. Patent Publication2014/0303697). In general, the systems provide a cooling contact surfaceconfigured to contact and freeze skin tissue (typically the superficiallayer of skin down to the dermal/epidermal junction). The freezing ofthe skin tissue may decrease melanin production, decrease melanosomeproduction, destroy meloncytes, and/or inhibit transfer of melanosomeinto keratinocytes in the lower region of the epidermal layer, therebyleading to skin lightening (i.e., hypopigmentation) for a period of timeor permanently.

Some treatments may use relatively modest skin cooling to temperaturesin the range of 0° C. to −20° C. over fairly short times frames, e.g.,as short as 15 seconds or less and up to 2 minutes or more. In someembodiments, skin cooling may be performed by controlling thetemperature of an aluminum plate (e.g. cooler) and applying the coolerdirectly to the skin—thereby cooling the skin through thermal conductionfrom the skin to the cooler.

It has been observed that in some instances, cooling treatments (e.g.,at −5 to−10 deg. C.) may lead to local supercooling of the skin, wherethe tissue does not freeze. Supercooling of the tissue alone may beinsufficient to result in hypopigmentation or may extend the length oftreatment. Accordingly, embodiments of the present invention help reduceor limit the occurrence of tissue supercooling during a coolingtreatment for hypopigmentation.

In some embodiments, a coupling fluid may be provided between thecontact surface of the treatment system and the skin. The coupling fluidmay be water or may be another fluid that freezes near 0 deg. C. Thefluid may include ice nucleating agents (INAs) to reduce supercoolingand to facilitate freezing of the tissue. The ice nucleating agents maybe organic (e.g., proteins, lipoproteins, bacteria, fungi, etc.) orinorganic (e.g., dust, soot, Silver Iodine, etc.). In some embodiments,the coupling fluid may include long-chain aliphatic alcohols or aminoacids (e.g., L-aspartic acid or the like). In some aspects, the skin maybe pierced or abraded prior to or during the cooling treatment. Thepiercing or abrasion may create small holes in the epidermis and mayfacilitate ice crystal propagation from the coupling fluid into thesuperficial layers of the skin. In some embodiments, the fluid includesa thickening agent to increase the viscosity such that a uniform layermay be consistently applied. In other embodiments, the fluid is loadedin a carrier, such as a woven or nonwoven cloth so as to retain auniform layer of fluid at the interface. Fluid-loading may occur at thetime of treatment or carriers may be loaded and prepackaged for use.

FIG. 1 illustrates an exemplary treatment method 100 for alteringmelanin content or melanocytes in a skin of a patient according to someembodiments of the present invention. At 102, a treatment area of a skinof a patient may be identified. At 104, the treatment area may beabraded or pierced. At 106, a fluid carrier may be applied to thetreatment area. At 108, a coupling fluid may be applied to the fluidcarrier and the fluid carrier may retain at least a portion of thecoupling fluid at the treatment area 108. At 110, a contact surface of acooling treatment probe may be pre-treated with seed crystals. At 112,the contact surface of the cooling treatment probe may be contacted withthe treatment area while the coupling fluid is present at the treatmentarea to cool and/or freeze the skin at the treatment area. At 114,vibrations may be applied to the treatment area during the coolingtreatment to promote ice crystal formation in the coupling fluid and/orthe skin of the patient.

In some embodiments, the treatment area of a skin of a patient may be apigmentation blemish of the skin. The pigmentation blemish may includehyperpigmentation, freckles, birthmarks, liver spots, age spots, café aulait spots, and pigmentation blemishes such as melasma. In someembodiments, a pigmentation blemish may be a superficial blemish or ablemish in the epidermis, e.g., liver spots, birthmarks, freckles, orthe like. In further embodiments, the pigmentation blemish may be orinclude a blemish in the dermis, e.g., deep pigmentation blemishes suchas melasma or the like. Optionally, the treatment area may be an area ofskin where the patient would prefer overall lightening of a complexionof the skin.

In some embodiments, a skin surface of the identified treatment area maybe may be abraded or pierced 104. During a cooling treatment, ice maystart to form at the interface of a cooling treatment probe. In order tofreeze the skin, the ice may then need to propagate into the skin fromthe cooling probe interface. The epidermis, however, is generallyimpervious to water, although there are specialized areas such as sweatglands that are specifically designed to control the flow of moistureacross this barrier. It may be however that ice propagation is limitedacross the epidermis as the skin is cooled which could result insupercooling in the tissue. To limit this, small holes can be made inthe epidermis to allow ice to freely propagate across this barrier.Holes can be initiated by abrasions with a rough cloth, brush, luffa, orsponge, with a dermabrasion or microdermabrasion roller or system, witha laser, electroporation or with a number of additional techniques orcombinations thereof. For example, in some embodiments a dermarollerwith 0.5 mm needles may be used to manually pierce the dermis.Optionally, a dermapen may be used with a depth setting of about 0.5 mmwhich punches rather than rolls holes into the dermis. In someembodiments, the epidermis may be pierced. In some embodiments dermis isminimally pierced. Optionally, in some embodiments, various combinationsof abrasion or piercing of the skin may be performed. While abrading theskin or piercing the skin may be desired in some embodiments, it shouldbe understood that these steps may be absent or even avoided in otherembodiments of the present invention.

In some embodiments, freezing can be triggered more reliably byspecifying and maintaining a fluid at an interface between a coolingtreatment applicator and the skin. For example, in some embodiments,water may be the coupling fluid that can be used to reduce the thermalcontact resistance between a cooling probe applicator and the skin andthereby improve cooling. In some embodiments, the coupling fluid may bea solution, a suspension, an emulsion, a colloid or the like. Forexample, in some embodiments, the coupling fluid may contain athickening agent to increase viscosity. The thickening agent may behelpful to maintain the coupling fluid at the treatment site.

Some coupling fluids such as water however, may experience supercoolingbelow its typical freezing point under certain conditions. Accordingly,in some embodiments, substances can therefore be mixed with the couplingfluid to limit or reduce the chance of supercooling or otherwise promotefreezing. Some such substances that may limit the occurrence ofsupercooling or otherwise promote freezing include inorganic materialssuch as soot, dust, fine particulates, or silver iodide crystals. Othermaterials that can be added to a coupling fluid are organic substancessuch as proteins, lipoproteins, bacteria or fungi. For example, in someembodiments pseudomonas syringae may be included and act as an icenucleating agent. Optionally, long chain aliphatic alcohols and aminoacids, such as 1-aspartic acid can also be added to the water, or otherfluid, with a freezing point near 0° C., to reduce the chance ofsupercooling in the tissue. In some embodiments, it may be preferable ifthe additives do not significantly decrease the freezing point of thecoupling fluid. Water for example has a freezing point generally of 0°C. which is very near that of the skin tissue.

Freezing can additionally be encouraged by applying a carrier at theinterface. The fluid carrier may help retain the coupling fluid at thetreatment area. The fluid carrier may be a piece of gauze or anotherwoven or non-woven material that is saturated with the coupling fluid.The carrier may occupy some volume, but may allow the free transfer ofcoupling fluid across it. This carrier may help ensure that a desiredvolume of water or other fluid is present at the interface whichfacilitates freezing of the skin. In some embodiments, it may bepreferable if the fluid carrier is of uniform thickness. Optionally, thefluid carrier may be combined with a treatment probe. In manyembodiments, however, the fluid carrier and fluid may be individuallypackaged and provided as disposable parts. In some embodiments, a fluidcarrier may be applied to a pre-cooled applicator to temporarily attachthe fluid carrier to the applicator surface through at least partialfreezing of the coupling fluid. It should be understood that the use ofa fluid carrier is optional. In some embodiments of the presentinvention, controlled and predictable freezing of the skin of thepatient may be provided through the utilization of a coupling fluidalone, for example.

The cooling probe may optionally be the cooling treatment apparatusesdescribed in U.S. Patent Publication 2011/0313411, U.S. PatentPublication 2014/0303696, U.S. Patent Publication 2014/0303697, or U.S.Patent Publication 2015/0223975, the disclosures of which areincorporated herein by reference in their entirety. For example, FIG. 2Aillustrates a side cross-sectional view of an exemplary apparatus 10that can be used to produce a hypopigmentation in a skin tissueaccording to some embodiments of the present invention. The exemplaryapparatus 10 can include a contact element 11 provided in a thermalcommunication with a cooling arrangement 12. In certain exemplaryembodiments, the contact element 11 and the cooling arrangement 12 canbe formed at least in part from a single material. A control arrangement15 can optionally be provided and used to control certain aspects of thecooling arrangement 12, e.g., temperature, timed shutoff, etc. Thecooling arrangement 12, control arrangement 15, and/or contact element11 can optionally be provided within or affixed to a housing orhandpiece 13, as shown in FIG. 2A, e.g., to facilitate handling andpositioning of the apparatus 10. The exemplary apparatus 10 shown inFIG. 2A is not necessarily drawn to scale. For example, the relativedimensions of the cooling arrangement 12 and contact element 11 are notlimited to the proportions illustrated in the FIG. 2A. In furtherexemplary embodiments of the present disclosure, the contact element 11can be larger or smaller in width or cross-sectional area as compared tothe dimensions of the cooling arrangement 12.

The contact element 11 can include a distal (contact) surface 14 that isconfigured to contact a skin surface. The distal surface 14 can besubstantially flat. In further exemplary embodiments of the presentdisclosure, the distal surface 14 can be convex or concave to bettermatch the local shape of skin tissue being treated and/or to providegood thermal contact with the skin surface when the apparatus 10 isplaced on the area of the skin to be treated. In still further exemplaryembodiments of the present disclosure, the contact element 11 can bedetachable from the cooling arrangement 12, e.g., so that a plurality ofcontact elements 11 having different sizes, shapes, and/or surfacefeatures as described herein can be used with a single cooling element12.

The distal contact surface 14 can have a large width or diameterconfigured to contact the surface of a region of skin, e.g., a diameteror width that is greater than about 3-10 cm, or greater than about 5 cm,to facilitate treatment of large areas of skin. In further embodiments,the width of the distal surface 14 can be small, e.g., on the order of1-2 cm or less, which may facilitate improved temperature control and/ortreatment of particular features on the skin.

The contact element 11 can be formed from a metal or a metal alloy, oranother material having a high thermal effusivity, e.g., such thatvalues of these thermophysical properties are greater than thecorresponding values for skin tissue. The thermal effusivity c is equalto the square root of the product of a material's thermal conductivityand its volumetric heat capacity. The thermal effusivity is a measure ofthe ability of a material to exchange heat with its surroundings and tomaintain a consistent temperature as it does so. For example, theinterface temperature T_(i) where two semi-infinite materials attemperature T₁ and T₂, respectively, are brought into contact willdepend on their relative effusivities, ε₁ and ε₂, asT_(i)=T₁+(T₂−T₁)*[ε₂/(ε₂+ε₁)]. Accordingly, e.g., with ε₂>>ε₁, theinterface temperature where the two materials are in contacts willremain close to T₂ as heat flows from one to the other. In this manner,the surface of a first material will be cooled down close to thetemperature of a second material having a much higher thermal effusivitywhen the second material is brought into contact with the firstmaterial.

For example, the contact element 11, at least in part or wholly, can bemade of brass, copper, silver, aluminum, an aluminum alloy, steel,graphite, diamond, diamond-like carbon, other materials which are usedin conventional contact cryoprobes, or combinations thereof. Forexample, the contact element 11 can be formed, wholly or at least inpart, from materials having a much higher thermal conductivity than theskin tissue, and can be used to facilitate an extraction of heat fromthe portion of the tissue contacted by the distal surface 14 of thecontact element 11. Further, materials having a much higher thermaleffusivity than the skin tissue, e.g. at least about 10 times thethermal effusivity of skin, can be more readily maintained at a coldtemperature. Such high-effusivity materials thereby may extract heatmore effectively from the portion of tissue contacted by the contactelement 11 than materials having lower thermal effusivities, andfacilitate a better control of the tissue temperature at a contactinterface.

In certain exemplary embodiments of the present disclosure, the distalcontact surface 14 of the contact element 11 can be smaller in area thanthe proximal end of the contact element 11 that contacts the coolingarrangement 12. Such geometry can provide certain advantages. Forexample, the narrower or tapered distal end of the contact element 11can facilitate a more precise placement of the distal surface 14 on aparticular location of the skin surface to be cooled, e.g., whilereducing visual obstruction by the housing 13. Further, the relativelylarger proximal end of the contact element 11 can provide a larger areathat can be directly cooled by the cooling arrangement 12 to facilitateincreased extraction of heat from the smaller distal contact surface 14.In certain embodiments, the area of the proximal end of the contactarrangement distal contact surface 14 can be at least twice as large asthe area of the distal contact surface 14, e.g., 3-5 times as large.

The distal surface 14 of the contact element 11 can be provided with aplurality of dimples 21, e.g., indentations or pockets formed in thecontact surface 14 of the contact element 11, as shown in thecross-sectional side view of FIG. 2A. Such dimples 21 can besubstantially round and have a diameter or width that is between about0.3 mm and about 3 mm, or between about 0.5 mm and 2 mm, or optionallyabout 1 mm. The depth of the dimples can be between about 0.3 mm andabout 2 mm, or between about 0.5 mm and about 1.5 mm, or optionallyabout 1 mm. The edges of the distal surface 14 can be rounded orbeveled, as shown in FIG. 2A, which can facilitate continuous contact ofthe distal surface 14 with the skin surface while avoiding contact withany sharp or abrupt edges or corners when the apparatus 10 is placedagainst the skin surface for treatment.

An exemplary end view of the contact surface 14 with dimples 21 is shownin FIG. 2B. An area fraction of the dimples 21 on the contact surface 14can be e.g., between about 0.05 and about 0.50, or optionally betweenabout 0.10 and about 0.30, or about 0.20. Such exemplary ranges andvalues of fractional area coverage can provides a sufficient area ofdirect skin contact by the contact surface 14 while also providingsufficient areal density of dimples 21 to improve local cooling and/orfreezing efficacy to generate hypopigmentation effects.

Although the size and depth of the exemplary dimples shown in FIGS. 2Aand 2B are substantially uniform, individual dimple sizes and/or depthsassociated with a single contact element 11 can vary within the rangesdescribed herein in further embodiments of the disclosure.

The exemplary arrangement of the dimples 21 on the contact surface 14can be substantially random, as shown in FIG. 2B. In a further exemplaryembodiment of the present disclosure, shown in FIG. 2C, the dimples 21can be provided in a radial arrangement. Such exemplaryarrangement/configuration can yield a lower density of dimples 21 (e.g.,a wider average spacing between adjacent dimples 21), which may lead toa reduced effect of the dimples 21 near the perimeter of the contactsurface 14. In a still further embodiment, the dimples 21 can beprovided in a regular array, e.g., a hexagonal array as shown in FIG.2D, or a square array.

In further exemplary embodiments of the present disclosure, the dimples21 can have an elongated shape, as shown in the exemplary configurationin FIG. 2E. Such elongate dimples 21 can have a smaller dimension (e.g.,width) that is between about 0.5 mm and about 3 mm, or optionally about1 mm. A longer dimension (e.g., length) of such elongate dimples 21 canbe greater than the width, e.g., twice the width or longer. For example,the exemplary dimples 21 shown in FIG. 2E have a length that is aboutfive times greater than the width. Other exemplary length-to-widthratios can be provided in further exemplary embodiments of the presentdisclosure. The depth of the elongate dimples 21 can be between about0.3 mm and about 2 mm, or between about 0.5 mm and about 1.5 mm, oroptionally about 1 mm. The edges of the distal surface 14 can be roundedand/or beveled where these dimples 21 meet the contact surface 14, asshown in FIG. 2A.

The long axes or dimensions of the exemplary elongate dimples 21 shownin FIG. 2E can be substantially parallel to one another. In a stillfurther exemplary embodiment of the present disclosure, the long axes ofsome elongate dimples 21 can be substantially perpendicular to otherones, e.g., as shown in FIG. 2F. In still further exemplary embodimentsof the present disclosure, the long axes of the elongate dimples 21 canbe provided at various angles to one another on the contact surface 14.The elongate dimples 21 can be provided in a regular array or pattern,as shown in FIGS. 2E and 2F. Alternatively or in addition, the elongatedimples 21 can be provided in a non-uniform or random arrangement, asshown, e.g., in FIG. 2G.

In further exemplary embodiments of the present disclosure, individualones of the dimples 21 provided on a single distal contact surface 14can have different sizes, shapes, and/or orientations. For example,different ones of the elongate dimples 21 can have the same width (smalldimension) and different aspect ratios (e.g., ratios of length to width)as shown, e.g., in FIG. 2H. In further exemplary embodiments of thepresent disclosure, different ones of the dimples 21 can have differentwidths and/or different lengths from one another as shown, e.g., in FIG.2I. In still further exemplary embodiments of the present disclosure,the contact surface 14 can include both round and elongate dimples 21 asshown, e.g., in FIG. 2J. In general, it can be preferable that the width(or diameter) and depth of the various dimples 21 are within the sizeranges described herein. In yet another exemplary embodiment of thepresent disclosure, elongate dimples 21 can be provided as a pluralityof substantially parallel grooves, as shown, e.g., in FIG. 2K. The endsof such dimples 21 can lie within the perimeter of the contact surface14 as shown in the exemplary configuration of FIG. 2K. Alternatively,the elongate dimples 21 can extend through the perimeter of the contactsurface 21, such that at least some of the dimples 21 form continuousgrooves that span the full length of the contact surface 14.

The interior surface of a dimple 21 can be rounded, cylindrical, orsquare in profile, or have another shape. For example, the interiorsurface of a round dimple 21 can be cylindrical or can have the shape ofa portion of a sphere or an ellipsoid. The interior surface of anelongate dimple 21 can have a shape that is rounded, such as a portionof a circular or ellipsoidal cylinder, or it may be provided withinternal corners, e.g., as a squared off channel or the like.

In general, a nearest distance between adjacent ones of the dimples 21at the contact surface can be at least as large as the width of thedimples 21. This exemplary distance between adjacent dimples 21 can begreater than their width, e.g., as shown in FIGS. 2B-2K. Such separationdistances can facilitate sufficient heat extraction from the vicinity ofeach dimple 21 and provide a sufficient area of the contact surface 14between dimples 21 so the contact surface 14 can be placed comfortablyagainst the skin surface.

The shape of the exemplary contact surface 14 shown in FIGS. 2B-2K issubstantially round. In a further exemplary embodiment of the presentdisclosure, the contact surface 14 can be provided with a shape that issubstantially square, rectangular, or hexagonal. Such shapes canfacilitate treatment of larger areas of skin by successively contactingadjacent areas thereof with the contact surface 14 while reducing oravoiding significant overlap in treated areas. In further embodiments,the contact surface 14 can have still different shapes.

The aspect ratio of the contact surface shape can be varied in differentexemplary embodiments. For example, a square, rectangular or hexagonalshape of the contact surface 14 can facilitate uniform coverage of alarger area of skin tissue by sequential placement of the apparatus 10on adjacent regions of skin tissue, such that substantially all of thedesired treatment area of skin has been cooled by the apparatus 10 withlittle or no overlap of such treatment regions. Other exemplary plateshapes and/or sizes can also be provided, e.g., to conform to particularregions of skin and/or to conform to a shape of a particular skinfeature to be treated such as, e.g., an age spot or the like.

One or more of any of the exemplary dimple shapes, dimensions, dimplepatterns, contact surface sizes and shapes, etc., or combinationsthereof, can be used with any of the exemplary embodiments and featuresof the present disclosure. For example, a single contact surface 14 caninclude a plurality of dimple shapes (e.g. round, elongated, etc.),spatial arrangements, etc., and certain various ones of such dimples 21provided on a single contact surface 14 can have one or morecharacteristic diameters, widths and/or depths, as described herein.

While not illustrated, it should be understood that in otherembodiments, the distal surface of the contact element 11 may be asmooth surface (e.g., not dimpled and without protrusions). A smoothdistal surface of contact element 11 may or may not be roughened. Insome embodiments, a smooth distal surface may be textured or roughenedin order to help capture or retain ice crystals duringtreatment—including cleaning and/or pre-treatment (described in furtherdetail below).

In some embodiments of the present invention, the contact surface of thecooling treatment probes may be pre-treated with seed crystals. As setforth above, the occurrence of supercooling may be limited or reduced bypresenting an ice nucleating agent which serves as a nucleation sourcefor the coupling fluid at or just below its freezing point. In someembodiments, the seed crystal may be frozen water, or ice (or frozencoupling fluid). It has been observed that when the applicator surfaceis cleaned with alcohol just prior to cooling skin, supercooling is morelikely. It is speculated that the alcohol slows or eliminates icenucleation on the applicator surface and thereby reduces or eliminatesavailable ice crystals on the applicator surface. Accordingly, in someembodiments, the contact surface of a cooling treatment probe may besprayed with a mist of water or other liquid, which will freeze on thecontact surface prior to the treatment to ensure that the applicator hasice crystals. In some embodiments, it may be helpful to allow theapplicator surface to dwell at a temperature below freezing for a periodof time prior to the treatment to ensure water from the air freezes onthe contact surface. In some embodiments, a dwell time may be 0.5-3minutes, preferably 1-2 minutes in typical environments. Dwell times maybe dependent, in-part, on ambient humidity where longer dwell times maybe preferable in drier environments.

In further embodiments, the contact surface may be textured to includegrooves or depressions to retain ice crystals even after being cleanedwith alcohol or other cleaners. Optionally, the contact surface mayinclude a rough texture that may harbor ice crystals or that may helpseed ice crystal formation. In some embodiments, the contact surface mayhave an R_(a) of 64 μm or greater (e.g., 64-128 μm or more), andpossibly 1000-2000 μm further embodiments. In certain embodiments, thecontact surface may be knurled. The knurled surface may have groovesthat are 0.1-0.8 mm deep. In addition these recessed areas prevent theice from melting when first applied to warm skin.

The contact surface of the cooling treatment probe may be contacted withthe treatment area while the coupling fluid is present at the treatmentarea 112. The cooling treatment may promote ice crystal formation in thecoupling fluid. The ice crystal formation in the coupling fluid may thenpropagate into the skin of the patient to freeze the skin. As set forthabove, the skin abrasion or piercing or the like, the coupling fluidwith or without ice nucleating agents, the use of fluid carriers, thepretreatment of a contact surface of a cooling treatment probe, and/orthe utilization of a treatment probe with a textured or roughenedcontact surface may limit supercooling or otherwise promote freezing ofthe skin of the patient during the cooling treatment and may therebyprovide more consistent skin freezing treatments.

While the treatment apparatuses described in U.S. Patent Publication2011/0313411, U.S. Patent Publication 2014/0303696, U.S. PatentPublication 2014/0303697, or U.S. Patent Publication 2015/0223975 may beused with embodiments of the present invention, in further embodimentsof the invention, the cooling treatment probe may include one or morevibrators for vibrating a contact surface of the cooling treatmentprobe. The vibrations or other kinds of mechanical perturbationsgenerated by the cooling treatment probe may help trigger or otherwisefacilitate or promote ice nucleation in the fluid medium and/or the skinof the patient. In some embodiments, acoustic transducers or ultrasoundmay be incorporated in the system design to help control the nucleationevent. Accordingly in some embodiments, the vibrator may include one ormore acoustic or ultrasound transducers (piezo elements or the like).The ultrasound transducer may deliver acoustic energy in the 20-100 kHzrange. Optionally the vibrator may be an electrical motor with anunbalanced mass on its drive shaft. While a cooling treatment probe withan integrated vibrator or ultrasound transducer may be beneficial insome embodiments, it should be understood that cooling treatment probeswithout vibrators may be used in other embodiments.

While method 100 is described above with specificity, it should beunderstood that some steps are optional and may be excluded in otherembodiments of the invention. For example, while coupling fluids with orwithout ice nucleating agents and/or thickening agents may be desired insome embodiments, other embodiments of the cooling treatment may beperformed without the coupling fluids. Additionally, the order of thesteps presented above is by no way limiting. Other embodiments of thetreatment method may perform steps in different orders and combinationsas desired.

FIGS. 3-6 illustrate a treatment of a treatment area 200 of a skin 202of a patient. The treatment area 200 may be a freckle, birthmark, liverspot, age spot, café au lait spot, or pigmentation blemishes such asmelasma or the like. The skin 202 includes a dermal layer 204 and anepidermal layer 206. In some embodiments, the methods and systemsdescribed herein provide freezing of the skin tissue down to thedermal/epidermal junction 208. The freezing of the skin tissue maydecrease melanosome production, destroy melanocytes, and/or inhibit thetransfer of melanosome into keratinocytes in the lower region of theepidermal layer, thereby leading to skin lightening.

FIG. 3 illustrates the application of a fluid carrier 210 to a skin 202of a patient according to some embodiments of the present invention. Thefluid carrier 210 may be a piece of gauze or another woven or non-wovenmaterial as described above. The fluid carrier 210 may help retain anamount of coupling fluid at the treatment area 200.

FIG. 4 illustrates the application of a coupling fluid 212 having icenucleating agents or thickening agents 214 according to some embodimentsof the present invention. Optionally, the coupling fluid 212 may beapplied to the area using a syringe or infusion cannula 216 in someembodiments. The coupling fluid may be water or another fluid. The icenucleating agents may be organic (e.g., bacteria, fungi, proteins, etc.)or inorganic (e.g., dust, soot, silver iodine, etc.). Thickening agentsmay be used (e.g., starch or the like) to increase the viscosity of thecoupling fluid 212 so as to limit the amount of runoff of the couplingfluid 212 from the treatment area 200.

FIG. 5 illustrates a cooling treatment applied by an exemplary coolingtreatment probe 218 to freeze at least a portion of the skin 202according to some embodiments of the present invention. The coolingtreatment probe 218 includes a cooling contact surface 220. The coolingcontact surface 220 may be cooled to a treatment temperature (e.g., −20to 0° C.; −10 to −2° C.). Optionally, the cooling contact surface 220may be pretreated by being cooled to the treatment temperature for athreshold duration of time (e.g., 20 seconds-2 minutes) prior totreatment such that moisture in the air forms seed crystals on thecontact surface 220 prior to application of the contact surface 220 withthe treatment area 200. In low humidity situations, the cooling contactsurface 220 may be pretreated by misting or otherwise applying a fluidonto the contact surface 220 so that the applied on fluid forms icecrystals on the contact surface 220. In some embodiments, the coolingcontact surface 220 may have a textured or roughened surface. Thetextured or roughened surface of contact surface 220 may limit theamount of supercooling of the skin 202 of the patient. In someembodiments, the cooling treatment probe 218 may further include one ormore vibrators 222. The one or more vibrators 222 may be ultrasoundtransducers or the like and may vibrate or mechanically perturb thecontact surface 220 of the cooling treatment probe 218 to limitsupercooling or otherwise promote freezing of the skin 202 of thepatient. In some embodiments, the contact surface 220 promotes icecrystal formation 224 in skin 202 of the patient with the assistance ofthe textured surface of the contact surface 220, the coupling fluid 212,the ice nucleating agents 214, and/or the vibrators 222. For example,the contact surface 220 may promote ice crystal formation 226 in thecoupling fluid 212 (and in fluid carrier 210). Ice crystal formation 226in the coupling fluid 212 may then progress through the skin 202 topromote ice crystal formation 224 in the epidermal layer 206.

FIG. 6 illustrates a reduction in melanin in the epidermal layer 206 ofthe skin 202 after ice crystal formation 224 in the epidermal layer 206according to some embodiments of the present invention.

FIGS. 7-10 illustrate a treatment of a treatment area 300 of a skin 302of a patient. The treatment area 300 may be a freckle, birthmark, liverspot, age spot, café au lait spot, or pigmentation blemishes such asmelasma or the like. The skin 302 includes a dermal layer 304 and anepidermal layer 306. In some embodiments, the methods and systemsdescribed herein provide freezing of the skin tissue down to thedermal/epidermal junction 308. The freezing of the skin tissue maydecrease melanin production, decrease melanosome production, destroymelanocytes, and/or inhibit the transfer of melanosome intokeratinocytes in the lower region of the epidermal layer, therebyleading to skin lightening.

FIG. 7 illustrates exemplary abrasion or piercing of the skin 302 of thepatient prior to treatment according to some embodiments of the presentinvention. Holes 309 can be introduced by abrasions with a rough clothor brush, with a microderm abrasion roller or system, with a laser, orwith a number of additional techniques (e.g., sandpaper or the like).FIG. 8 illustrates the application of a coupling fluid 312 to thetreatment area 300 of the skin 302 according to some embodiments of thepresent invention. While not essential, in some embodiments, icenucleating agents or thickening agents may be added to the couplingfluid 312. As illustrated, the coupling fluid 312 may penetrate a depthinto the epidermal layer 306 of the skin 302 of the patient with theabrasion/piercing of the skin 302 prior to treatment.

FIG. 9 illustrates a cooling treatment applied by an exemplary coolingtreatment probe 318 to freeze at least a portion of the skin 302according to some embodiments of the present invention. Coolingtreatment probe 318 may be similar to cooling treatment probe 218. Whilea textured contact surface and/or vibrators may be beneficial forpromoting ice formation in the skin 302 of the patient, other coolingtreatment probes may be used, such as those described in U.S. PatentPublication 2011/0313411, U.S. Patent Publication 2014/0303696, U.S.Patent Publication 2014/0303697, or U.S. Patent Publication2015/0223975, previously incorporated by reference.

The cooling treatment probe 318 may promote ice crystal formation 326 inthe coupling fluid 312. Thereafter, the ice crystal formation 326 mayprogress through the holes 309 created in the skin 302 and into theepidermal layer 306. The ice crystal formation in the epidermal layermay lead to a reduction in melanin and/or melanocytes in the epidermallayer 306 of the skin of the patient as illustrated in FIG. 10.

FIG. 11 illustrates an exemplary cross-sectional side view of anexemplary cooling treatment apparatus 400 that can be used to producehypopigmentation in a skin tissue according to some embodiments of thepresent invention. The exemplary apparatus 400 can include a coolingapplicator 411 provided in a thermal communication with a thermoelectriccooler 412. A heat exchanger 416 may be thermally coupled with thethermoelectric cooler 412 on a side opposite from the cooling applicator411. In certain exemplary embodiments, the cooling applicator 411 andthe cooling arrangement 412 can be formed at least in part from a singlematerial. As discussed above, a vibrator 418 (e.g., acoustic transducer,ultrasound transducer, or the like) may be provided. In someembodiments, the ultrasound transducer 418 may be coupled with a distalside of the heat exchanger 416 so that the ultrasound transducer 418 ison the opposite side of the heat exchanger 416 relative to the thermalelectric cooler. A controller 415 can be provided and used to controlcertain aspects of the thermoelectric cooler 412, e.g., temperature,etc. Additionally, the controller 415 may be coupled with the ultrasoundtransducer 418 to control the delivery (e.g., timing, power, frequency,etc.) of the ultrasound from the ultrasound transducer 418. Thethermoelectric cooler 412, controller 415, ultrasound transducer 418,and/or cooling applicator 411 can optionally be provided within oraffixed to a housing or handpiece 413, as shown in FIG. 11, e.g., tofacilitate handling and positioning of the apparatus 400. The exemplaryapparatus 400 shown in FIG. 11 is not necessarily drawn to scale.

For example, the relative dimensions of the thermoelectric cooler 412and cooling applicator 411 are not limited to the proportionsillustrated in the FIG. 11. In further exemplary embodiments of thepresent disclosure, the cooling applicator 411 can be larger or smallerin width or cross-sectional area as compared to the dimensions of thethermoelectric cooler 412.

The cooling applicator 411 can include a distal (contact) surface 14that is configured to contact a skin surface. The distal surface 414 canbe substantially flat. In further exemplary embodiments of the presentdisclosure, the distal surface 414 can be convex or concave to bettermatch the local shape of skin tissue being treated and/or to providegood thermal contact with the skin surface when the apparatus 400 isplaced on the area of the skin to be treated. In still further exemplaryembodiments of the present disclosure, the cooling applicator 411 can bedetachable from the thermoelectric cooler 412, e.g., so that a pluralityof cooling applicator 411 having different sizes, shapes, and/or surfacefeatures as described herein can be used with a single thermoelectriccooler 412.

The distal contact surface 414 can have a large width or diameterconfigured to contact the surface of a region of skin, e.g., a diameteror width that is greater than about 3-10 cm, or greater than about 5 cm,to facilitate treatment of large areas of skin. In further embodiments,the width of the distal surface 414 can be small, e.g., on the order of1-2 cm or less which may facilitate improved temperature control and/ortreatment of particular features on the skin.

The subject matter of the present invention is described here withspecificity, but the claimed subject matter may be embodied in otherways, may include different elements or steps, and may be used inconjunction with other existing or future technologies.

This description should not be interpreted as implying any particularorder or arrangement among or between various steps or elements exceptwhen the order of individual steps or arrangement of elements isexplicitly described. Different arrangements of the components depictedin the drawings or described above, as well as components and steps notshown or described are possible. Similarly, some features andsub-combinations are useful and may be employed without reference toother features and sub-combinations. Embodiments of the invention havebeen described for illustrative and not restrictive purposes, andalternative embodiments will become apparent to readers of this patent.Accordingly, the present invention is not limited to the embodimentsdescribed above or depicted in the drawings, and various embodiments andmodifications may be made without departing from the scope of the claimsbelow.

What is claimed is:
 1. A method of altering pigmentation in a skin of apatient, the method comprising: applying a coupling fluid to a treatmentarea on the skin of the patient, the coupling fluid including an icenucleating agent configured to promote ice formation in the couplingfluid; applying a cooling treatment to the treatment area with theapplied coupling fluid present, wherein the cooling treatment promotesice crystal formation in the coupling fluid and wherein the ice crystalformation in the coupling fluid propagates into the skin of the patientduring the cooling treatment.
 2. The method of claim 1, wherein the icenucleating agent comprises a bacteria, a fungi, soot, or dust.
 3. Themethod of claim 1, wherein the ice nucleating agent comprises a protein,lipoprotein, or a long-chain aliphatic alcohol or amino acid.
 4. Themethod of claim 1, further comprising abrading or piercing the treatmentarea prior to applying the cooling treatment.
 5. The method of claim 4,wherein abrading or piercing the treatment area comprises abrading orpiercing the treatment area using a microderm abrasion roller or alaser.
 6. The method of claim 1, wherein applying the coupling fluid tothe treatment area on the skin of the patient comprises applying a fluidcarrier to the treatment area of the skin, the fluid carrier configuredto retain the coupling fluid at the treatment area.
 7. The method ofclaim 6, wherein the fluid carrier has a uniform thickness.
 8. Themethod of claim 6, wherein the fluid carrier comprises a fabricmaterial.
 9. The method of claim 1, wherein the coupling fluid comprisesan aqueous fluid comprising a thickening agent that increases viscosityof the aqueous fluid.
 10. The method of claim 1, wherein applying thecooling treatment comprises contacting a treatment surface of a coolingprobe with the coupling fluid at the treatment site, wherein the coolingprobe comprises a vibrator for facilitating ice formation.
 11. Themethod of claim 10, wherein the vibrator comprises an ultrasoundtransducer.
 12. The method of claim 1, wherein applying the coolingtreatment comprises contacting a treatment surface of a cooling probewith the coupling fluid at the treatment site, wherein the treatmentsurface of the cooling probe comprises a textured surface havingrecessed areas configured to retain ice crystals.
 13. A method ofaltering pigmentation in a skin of a patient, the method comprising:applying a fluid carrier and a coupling fluid to a treatment area on theskin of the patient, the fluid carrier retaining the coupling fluid atthe treatment area; applying a cooling treatment to the treatment areaof the skin to promote ice crystal formation in the coupling fluidretained by the fluid carrier, and wherein the ice crystal formation inthe coupling fluid propagates into the skin of the patient during thecooling treatment.
 14. The method of claim 13, further comprisingabrading or piercing the treatment area prior to applying the coolingtreatment.
 15. The method of claim 13, wherein the fluid carrier has auniform thickness.
 16. The method of claim 13, wherein the fluid carriercomprises a fabric material.
 17. A method of altering pigmentation in atarget area of a skin of a patient, the method comprising: abrading orpiercing an epidermis layer of a skin defining a target area; applying acoupling fluid to the target area on the skin of the patient; applying acooling treatment to the treatment area with the applied coupling fluidpresent, wherein the cooling treatment promotes ice crystal formation inthe coupling fluid and wherein the ice crystal formation in the couplingfluid propagates into the skin of the patient during the coolingtreatment.
 18. A method of altering pigmentation in a target area of askin of a patient, the method comprising: pre-treating a contact surfaceof a cooling treatment probe by misting a liquid on the contact surface,wherein the misted liquid forms ice crystals on the contact surface ofthe cooling treatment probe; applying a fluid carrier to a treatmentarea on the skin of the patient; contacting the pre-treated contactsurface of the cooling treatment probe with the coupling fluid at thetreatment site, wherein the cooling treatment probe promotes ice crystalformation in the coupling fluid and wherein the ice crystal formation inthe coupling fluid propagates into the skin of the patient during thecooling treatment.
 19. A method of altering pigmentation in a targetarea of a skin of a patient, the method comprising: contacting atreatment surface of a cooling probe to the target area of the skin ofthe patient, the cooling probe configured to deliver a cooling treatmentto promote ice crystal formation in the skin of the patient; wherein thecooling probe includes a vibrator for delivering vibrations to the skinto facilitate ice formation in the skin during the cooling treatment.20. The method of claim 19, wherein the vibrator comprises an ultrasoundtransducer.
 21. The method of claim 20, wherein the ultrasoundtransducer is configured to deliver an ultrasound pulse at an acousticenergy in the 20-100 kHz range.
 22. The method of claim 19, wherein thevibrator comprises an acoustic transducer.
 23. The method of claim 19,wherein the vibrator comprises a motor with an unbalanced mass on adrive shaft of the motor.
 24. A system for altering pigmentation in askin of a patient comprising: a cooling treatment probe comprising acontact surface for contacting a treatment area of the skin of thepatient with a coupling fluid present at the treatment area, the contactsurface having a textured surface having recessed areas configured topromote ice crystal formation in the coupling fluid during a coolingtreatment and the ice crystal formation in the coupling fluid configuredto propagate into the skin of the patient during cooling treatment. 25.The system of claim 24, wherein the cooling treatment probe comprises avibrator for vibrating the contact surface of the cooling treatmentprobe to facilitate ice formation.
 26. The system of claim 25, whereinthe vibrator comprises an ultrasound transducer.
 27. The system of claim24, further comprising the coupling fluid, the coupling fluid includingan ice nucleating agent for application to the treatment area of theskin of the patient.
 28. The system of claim 27, wherein the icenucleating agent comprises a bacteria, a fungi, soot, or dust.
 29. Themethod of claim 27, wherein the ice nucleating agent comprises aprotein, lipoprotein, or a long-chain aliphatic alcohol or amino acid.30. The system of claim 24, further comprising a fluid carrier forapplication to the treatment area and for retaining coupling fluid atthe treatment area.
 31. The system of claim 30, wherein the fluidcarrier has uniform thickness.
 32. The system of claim 30, wherein thefluid carrier comprises a fabric material.
 33. A system for alteringpigmentation in a skin of a patient comprising: a fluid carrierconfigured to be applied to a treatment area of the skin and configuredto be infused with a coupling fluid and configured to retain thecoupling fluid at the treatment area of the skin; a cooling treatmentprobe comprising a contact surface for contacting the fluid carrier, thecontact surface of the cooling treatment probe configured to promote icecrystal formation in the coupling fluid retained in the fluid carrier.34. The system of claim 33, wherein the fluid carrier has uniformthickness.
 35. The system of claim 33, wherein the fluid carriercomprises a fabric material.
 36. A system for altering pigmentation in askin of a patient comprising: a cooling treatment probe comprising acontact surface for contacting a treatment area of the skin of thepatient to apply a cooling treatment to the skin, and a vibrator forvibrating the contact surface of the cooling treatment probe duringcooling treatment application.
 37. The system of claim 36, wherein thevibrator comprises an ultrasound transducer.
 38. The system of claim 37,wherein the ultrasound transducer is configured to deliver an ultrasoundpulse at an acoustic energy in the 20-100 kHz range.
 39. The system ofclaim 36, wherein the vibrator comprises an acoustic transducer.
 40. Thesystem of claim 36, wherein the vibrator comprises a motor with anunbalanced mass on a drive shaft of the motor.